Pelvic inflammatory disease (PID)
is one of the most common complications of sexually transmitted infections in
women. It affects various structures of the upper female genital tract,
leading to disorders such as endometritis, salpingitis, tubo-ovarian abscess,
and pelvic peritonitis.1 In the United States PID affects about 750,000 women
each year, causing infertility in about 10% to 15% of affected women.2 It can
lead to chronic pelvic pain and is also a major cause of ectopic pregnancy.2
PID presents with a wide clinical spectrum and often goes undetected because
signs and symptoms are non-specific; therefore, a low threshold for diagnosis
should be maintained.1

PID is often caused by sexually transmitted organisms, most commonly Chlamydia trachomatis and
Neisseria gonorrhoeae. Other causative organisms include
constituents of vaginal flora, such as anaerobic bacteria, Gardnerella vaginalis,
Haemophilus influenzae, enteric gram-negative rods, and Streptococcus agalactiae.2,3
Cytomegalovirus, Mycoplasma hominis, Mycoplasma genitalium, and Ureaplasma urealyticum have also been implicated
as causative agents.1-4

Chlamydia and gonorrhea are the 2 most common reportable sexually transmitted
infections in the United States.5
Each year an estimated 2.9 million new C trachomatis
infections occur among adolescents and adults in the United States6;
N gonorrhoeae is responsible for an estimated
820,000 new infections annually.6
These diseases affect both men and women and are often spread unknowingly by
asymptomatic individuals. Infection during pregnancy may result in neonatal
transmission, leading to complications such as ophthalmia neonatorum and
pneumonia.

Cure rates for chlamydial
infection are about 97% to 98% with a 7-day, multidose regimen of doxycycline
or a single dose of azithromycin.7N gonorrhoeae also responds well to
treatment, although resistance to beta-lactams, fluoroquinolones, and oral
cephalosporins can complicate response. Fluoroquinolones are not recommended
for treatment of gonorrhea, and oral cephalosporins are no longer recommended
as a first-line therapy.8
Because chlamydia is common in patients with gonorrhea, cotreatment should be
considered in individuals with diagnosed gonorrheal infection.8
See Centers for Disease Control and Prevention (CDC) guidelines for currently
recommended treatment regimens.8

Current guidelines recommend N gonorrhoeae and C
trachomatis testing, as well as HIV screening, for all women with
PID.1
Conversely, screening for N gonorrhoeae and
C trachomatis may also aid in detecting
subclinical PID or avoiding progression to PID. Subclinical PID has been
reported in >25% of women with gonorrhea or chlamydia9; some studies have
indicated that up to 40% of women with untreated chlamydia develop PID.10
Because most people with C trachomatis infection are asymptomatic and are not
aware of their infection, screening is important if these infections are to be
adequately diagnosed and treated. Chlamydia screening among asymptomatic,
sexually active women can decrease the incidence of PID11 and, possibly, the
prevalence of chlamydial infection. Screening for cervical C trachomatis
infection in asymptomatic women can be cost effective. Screening with a DNA
amplification assay, coupled with a single dose of azithromycin in positive
patients, was reported to be a cost-effective strategy when the prevalence is
6% or greater.12 Screening high-risk women and treating those infected was
found to significantly lower the incidence of PID relative to a control
population (9/1009 [0.9%] vs 33/1598 [2.1%], respectively).11
Similarly, an
economic evaluation of a school-based sexually transmitted infection program
in New Orleans revealed a savings of $1524 for each case of PID prevented.13
Thus, timely detection followed by effective therapy appears to be a
cost-effective way of preventing complications and further spread of C
trachomatis infection.

Guidelines from the CDC now
recommend routine annual chlamydia screening for all sexually active women
under 25 years of age and for all women at increased risk.1 Moreover, because
repeat infection is common in women with chlamydia, retesting should be
considered about 3 to 4 months after treatment.1 Targeted gonorrhea screening
among sexually active women at high risk for infection is also recommended
(see “Individuals Suitable for Testing” below).14

Chlamydia trachomatis RNA, TMA: This test
directly detects the presence of C trachomatis
ribosomal RNA (rRNA). It is based on transcription-mediated amplification
(TMA) and is highly sensitive and specific. The test can be performed on
either swab or urine specimens from men and women.

Chlamydia trachomatis RNA, TMA Alternate Target:
This test directly detects the presence of C
trachomatis ribosomal RNA (rRNA) using an alternate molecular
target than the routine Chlamydia trachomatis RNA, TMA assay. It can be
ordered to confirm an initial positive result. It is based on TMA and is
highly sensitive and specific. The test can be performed on either swab or
urine specimens from men and women.

Chlamydia trachomatis DNA, SDA: This test
directly detects the presence of C trachomatis
DNA. It is based on strand displacement amplification (SDA) and is highly
sensitive and specific. The test can be performed on either swab or urine
specimens from men and women. The test can also be performed on endocervical
specimens submitted in liquid-based Pap test vials.

Neisseria gonorrhoeae
RNA, TMA Alternate Target:
This test directly detects the presence of N gonorrhoeae rRNA using an alternate
molecular target than the routine Neisseria
gonorrhoeae RNA, TMA assay. It can be ordered to confirm an
initial positive result. It is based on TMA and is highly sensitive and
specific. The test can be performed on either swab or urine specimens from
men and women.

Neisseria gonorrhoeae RNA, TMA:
This test directly detects the presence of N
gonorrhoeae rRNA. It is based on TMA and is highly sensitive and
specific. The test can be performed on either swab or urine specimens from
men and women.

Neisseria gonorrhoeae DNA, SDA:
This test directly detects the presence of N
gonorrhoeae DNA. It is based on SDA and is both sensitive and
specific. The test can be performed on either swab or urine specimens from
men and women. The test can also be performed on endocervical specimens
submitted in liquid-based Pap test vials.

Non-nucleic Acid Tests

Chlamydia trachomatis Antigen, DFA:
The direct fluorescence antibody assay (DFA) directly detects the presence
of C trachomatis. This test is cleared for
conjunctiva specimens. Specimens are incubated with fluorescein-labeled
monoclonal antibody and examined microscopically for fluorescence of
chlamydial elementary bodies. Specimen quality is assessed by checking for
the presence of epithelial columnar cells.

Chlamydia trachomatis Culture: This test
detects the presence of C trachomatis. The
organism is grown in cell culture and then identified via an
immunofluorescence assay with monoclonal antibodies specific for the major
outer membrane protein (MOMP), present in all 15 known serovars of C trachomatis but not C
pneumoniae or C psittaci.

Neisseria gonorrhoeae Culture: This test
detects the presence of N gonorrhoeae.
Organisms are identified by biochemical characteristics and confirmed by a
molecular assay. Culture and susceptibility should be performed in cases of
suspected treatment failure.

Culture is no longer the standard for diagnosis of C
trachomatis infection. With the advent of nucleic acid
amplification and detection methods, culture is used infrequently because
of higher cost, specimen viability requirements during collection and
transport, and slow turnaround time (3–7 days). Culture continues to be
the most specific method (~100%), followed closely by nucleic acid
amplification assays. The remaining methods range from 97% to 99%
specific, depending on the study. The CDC recommends nucleic acid
amplification tests for detecting infection of the reproductive tract in
both men and women, regardless of symptoms.1

Non-culture tests for C trachomatis are more rapid and standardized and
have less stringent specimen handling requirements. Nucleic acid
amplification tests such as SDA and TMA are the most sensitive methods for
detecting C trachomatis.1 Compared with amplification methods, culture is
only 70% to 85% sensitive.16,17 The remaining tests are all less sensitive
than culture (sensitivity roughly 70%7–97% that of culture, depending on
reagent manufacturer and specimen type).

Chlamydia Test-of-Cure

Routine test-of-cure is not recommended for chlamydia when first-line
regimens are used.1 When test-of-cure is indicated, as in the case of
chlamydial infection during pregnancy, nucleic acid amplification testing
should be performed 3 weeks post-therapy.1
Non-culture detection methods should not be used <3 weeks after treatment
is completed.1

Gonorrhea

Nucleic acid amplification testing of endocervical, vaginal, male
urethral, or urine specimens can be used to detect of gonorrhea affecting
the genitourinary system.1
Culture and antimicrobial susceptibility testing should also be performed
when treatment failure is suspected.1

As with chlamydia testing, nucleic acid amplification assays for gonorrhea
offer convenience and high sensitivity. The difference in sensitivity
between culture and nucleic acid amplification methods is less pronounced
than with chlamydia, although inappropriate storage and transport
conditions can lessen the sensitivity of culture. SDA has shown
specificity similar to that of culture and greater sensitivity).18
TMA also exhibits excellent specificity (99% in swabs and urine) and
sensitivity (99% in swabs, 91% in urine).19

Positive results are considered evidence of infection.
Because of the high specificity of available molecular tests, confirmatory
testing is generally not necessary.20 However, in low
prevalence populations or in a case where a positive may have severe
socio-legal ramifications, testing with an alternate method or target is
recommended. Individuals positive for one STI should be tested for others.

Chlamydia

Antibody tests: C
trachomatis infection confers little immunity against reinfection,
although secretory IgA may provide some protection. A positive IgM
antibody result may indicate recent infection with C trachomatis; a
negative result, however, does not indicate absence of C trachomatis
since IgM antibodies are frequently absent in infected individuals.
The presence of IgG indicates active or resolved infection. High IgG
titers often point to recent infection, whereas intermediate or low titers
may be due to early infection, resolved infection, or cross-reaction with
other Chlamydia species. When comparing antibody tests, a 4-fold
rise in titer best indicates active infection. Serologic tests are not
recommended for chlamydia screening.3

Culture: A positive
culture result is highly specific for C trachomatis. A negative
result may indicate absence of C trachomatis infection or a
false-negative due to lack of organism viability or improper specimen
collection.

DFA: A positive DFA result
indicates the presence of C trachomatis infection, whereas a
negative result implies absence of infection or a false-negative due to
lack of assay sensitivity.

RNA, TMA: A positive TMA
result is highly indicative of C trachomatis infection, while a
negative result is highly indicative of lack of infection. False-positive
results may be obtained due to laboratory contamination (rare in an
experienced lab) or sampling too soon after cessation of therapy (ie, <3
weeks post-therapy).

DNA, SDA: A positive DNA
result is highly indicative of C trachomatis infection. False-positive
results may be obtained due to laboratory contamination (rare in an
experienced lab) or sampling too soon after cessation of therapy (ie, <3
weeks post-therapy). Negative results are highly specific for lack of C
trachomatis infection but may be caused by interfering substances.

Gonorrhea

Culture: A positive
culture result is highly specific for N gonorrhoeae. A negative result may
indicate absence of infection or a false-negative due to lack of organism
viability or improper specimen collection.

DNA, SDA: A positive test
result strongly suggests N gonorrhoeae infection. False-positive results
may be obtained due to laboratory contamination (rare in an experienced
lab) or sampling too soon after cessation of therapy (ie, <3 weeks
post-therapy). Negative results are highly specific for absence of N
gonorrhoeae infection but may be caused by interfering substances.

RNA, TMA: A positive TMA
result is highly indicative of N gonorrhoeae infection, while a negative
result is highly indicative of lack of infection. False-positive results
may be obtained due to laboratory contamination (rare in an experienced
lab) or sampling too soon after cessation of therapy (ie, <3 weeks
post-therapy).